Biobags, also known as cell culture bags or bio-reactive containers, are used, among other purposes, to culture cellular material in a sterile environment. To accomplish this intended purpose, gases or other fluids necessary to promote cell growth and division must be introduced into, and removed from, the biobag containers. A common bio-reactive container configuration, such as that shown designated generally as 7 in FIG. 15, includes a bag-like structure 1 made from pliable, flexible synthetic materials such as polyethylene or polypropylene to provide a substantially air-tight fluid-impermeable environment in which to grow and expand cell cultures in a sterile manner.
Access to the container inner chamber is provided commonly by at least one inlet port 2 and one outlet port 3. Containers may also have multiple inlet and outlet ports-some dedicated to liquids and others dedicated to gases. The ports are often formed as cylindrical appendages extending from the containers. Each port may be structured with connectors for connecting to fluid and/or gas sources and may be formed as integral or modular components of the containers. Means to block fluid and/or gas flow into and/or out of the container, e.g., check valves and the like, may be provided at each port. Liquids, e.g., sterilized water, nutrient fortified solutions and the like may be transferred into the container from the inlet side. Gases, e.g., oxygen for aeration, filtered air and nitrogenous-bearing gases and the like may also be transferred into the container to promote cell culture development.
Excess liquids and/or gasses introduced into the containers may require removal from the containers to further promote desired cell culture development. Gaseous and fluid-based byproducts and wastes derived from cellular respiration and the like may also require removal from the containers. Product(s) derived from the cellular activity within the containers and desired for harvesting will also need to be removed from the containers. One or more outlet ports may be provided to permit the removal of such substances.
One significant problem with bio-reactive containers is their sensitivity to fluid and/or gas pressure. Bio-reactive containers often have low burst pressure ratings on the order of about 1-5 psi and often have recommended operational pressures on the order of about 0.2-0.5 psi. Any significant fluid or gas pressure introduced into the containers, above the burst pressure limit, will likely lead to rupture or failure of the containers. To address this issue, one or more vent filters 5 may be secured to the containers with the appropriate flow rate versus pressure-drop performance to allow exhaust gas to escape without over-pressurizing the containers. The vent filter serves as a sterile barrier between the internal container chamber and the environment outside of the container so as to prevent microbial contamination from transferring from the internal chamber to the outside environment and vice versa. The filter also functions to prevent the egress of non-sterile liquids and/or gases depending upon the application.
It is similarly necessary to place a sterilizing device in the fluid and/or gas inlet lines. To accomplish the desired sterilizing effect, a filtering device 4 is often placed in the fluid and/or gas infusion lines downstream of a pump or regulator used to drive and control fluid flow upstream of the container. The inlet filter also serves as a sterile barrier between the internal container chamber and the environment outside of the container so as to prevent microbial contamination from transferring from the internal chamber to the outside environment and vice versa.
Due to the common tubular inlet and/or outlet configurations that can range from about 0.25 inches to about 1 inch in diameter, the filters used for this application are contained in filter capsules, e.g., filter capsule 6 for outlet filter 5, that include inlet and outlet ports dimensionally complimentary to the tube/piping and/or inlet systems of the bio-reactive containers and with appropriate connection fittings, such as barbed fittings, where necessary. The relatively small cross-sectional area of the inlet tubing systems creates a further limitation on fluid and/or gas flow rate and bulk mass transfer into the containers.
A similar flow-rate restriction is experienced on the outlet side of the bio-reactive container. Outlet ports, structured and dimensioned similar to the inlet ports, create a flow restriction with respect to liquids and/or gases removed from the containers. Filters incorporated into the outlet tube system also contribute to the flow restriction of liquids and/or gases. This may result in the development of unwanted backpressure that further impedes inlet flow and may compromise the speed and efficiency of cell culture formation as well as the production of desirable products derived from cell cultures.
Smaller capsules may incorporate flat-sheet filter membranes that are relatively low in cost, but limit the potential fluid-receiving surface area to less than 100 cm2. Applications requiring larger filter surface areas often incorporate pleated filter designs to increase surface area within a similar cross-sectional area. Pleated filters, however, increase cost and add undesirable weight to the bio-container. Further, in the case of exhaust gas exiting from the bio-container, the tubing commonly used to connect filters to the bio-container can present a problem when moisture contained in the humid gas condenses in the tubing. The formed liquid can make its way into the filter assembly and block the flow of air through the hydrophobic vent filter membrane.
What is needed is a bio-reactive container filter configuration that maintains low cost and significantly increases available filter surface area to maximize fluid flow rates. What is also needed is a filter configuration that permits the use of low fluid and/or gas pressures to protect container integrity without compromising fluid flow rates and/or mass transfer rates. What is further needed is a filter configuration that prevents the trapping of liquid within connective tubing and within the filter assembly itself. These and other objects of the disclosure will become apparent from a reading of the following summary and detailed description of the disclosure.